This SuperSeries is composed of the SubSeries listed below.
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesIn this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesIn this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesIn this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesWe comprehensively explored Fas expression (protein and mRNA) and function in lymphocyte activation, apoptosis, proliferation and transcriptome, using flow cytometry, [3H]-thymidine incorporation and microarray analysis in PBMC from HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) patients.
A Fas<sup>hi</sup> Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation.
Specimen part, Disease stage, Treatment
View SamplesMedullary breast cancers (MBC) display a basal profile, but a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive early breast adenocarcinomas. We developed a Support Vector Machine (SVM) classifier based on this 368-gene list in a learning set, and tested its predictive performances in an independent validation set. Then, we assessed its prognostic value and that of six prognostic signatures for disease-free survival (DFS) in the remaining 2034 samples. The SVM model accurately classified all MBC samples in the learning and validation sets. A total of 466 cases were basal across other sets. The SVM classifier separated them into two subgroups, subgroup 1 (resembling MBC) and subgroup 2 (not resembling MBC). Subgroup 1 exhibited 71% 5-year DFS, whereas subgroup 2 exhibited 50% (p=9.93E-05). The classifier outperformed the classical prognostic variables in multivariate analysis, conferring lesser risk for relapse in subgroup 1 (HR=0.52, p=3.9E-04). This prognostic value was specific to the basal subtype, in which none of the other prognostic signatures was informative.
A gene expression signature identifies two prognostic subgroups of basal breast cancer.
Age, Specimen part
View SamplesNitric oxide regulates plant development and responses to stress. However, the mechanisms underlying its regulatory role are still poorly known, and the impact of endogenous NO on the genome-wide transcriptome of plants has not been studied. For that purpose, we compared the transcriptomes of NO-deficient nia1nia2, noa1-2 and nia1nia2noa1-2 mutant versus wild type Arabidopsis thaliana plants. A core comprising 66 NO-responsive genes with similar expression in all NO-deficient genotypes was identified. Among them, 46 were down- and 20 up-regulated in NO-deficient plants, and thus positively and negatively regulated by endogenous NO, respectively. Accordingly with changes in its transcriptome, the NO-deficient nia1nia2noa1-2 mutant accumulated anthocyanins and indolic glucosinolates, displayed abnormal iron homeostasis in shoots and roots, and also showed altered root sensitivity to hormones such as ABA, ET, CYK and IAA. Together the presented data suggest NO functions essentially as a modulator of hormone action.
Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors.
Specimen part
View SamplesSenescence is a developmental process and chlorophyll is an indicator of leaf senescene. In plants cytokinin plays a role in delaying leaf senescence. Chlorophyll degradation is tightly regulated during senescence and cytokinin might interplay in the chrorophyll degradation pathway to regulate leaf greening.
Cytokinin delays dark-induced senescence in rice by maintaining the chlorophyll cycle and photosynthetic complexes.
Specimen part
View SamplesWe describe a case of severe neonatal anemia with kernicterus due to compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1 null human. The phenotype of severe DAT-negative non-spherocytic hemolytic anaemia (NSHA), jaundice, hepato-splenomegaly, and marked erythroblastosis is more severe than that present in CDA type IV due to dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis. Overall design: mRNA sequencing on peripheral blood from a family trio (mother, father and proband) where parents were asymptomatic and proband had severe neonatal anemia.
KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Specimen part
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